Retinoic acid as a novel medical therapy for Cushing's disease in dogs

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Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action i...

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Autores principales:	Castillo, V., Giacomini, D., Páez-Pereda, M., Stalla, J., Labeur, M., Theodoropoulou, M., Holsboer, F., Grossman, A.B., Stalla, G.K., Arzt, E.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2006
Materias:	alpha intermedin corticotropin creatinine hydrocortisone ketoconazole retinoic acid animal experiment animal model article controlled study corticotropin blood level creatinine urine level Cushing disease dog drug efficacy drug safety female hormone blood level hydrocortisone urine level hypophysis hypophysis adenoma male nonhuman nuclear magnetic resonance imaging priority journal survival tumor volume Adenoma Adrenocorticotropic Hormone alpha-MSH Animals Body Weight Creatinine Dog Diseases Dogs Female Hydrocortisone Ketoconazole Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Pituitary Gland Pituitary Neoplasms Survival Rate Tretinoin
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v147_n9_p4438_Castillo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00137227_v147_n9_p4438_Castillo
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spelling	paperaa:paper_00137227_v147_n9_p4438_Castillo2023-06-12T16:41:39Z Retinoic acid as a novel medical therapy for Cushing's disease in dogs Endocrinology 2006;147(9):4438-4444 Castillo, V. Giacomini, D. Páez-Pereda, M. Stalla, J. Labeur, M. Theodoropoulou, M. Holsboer, F. Grossman, A.B. Stalla, G.K. Arzt, E. alpha intermedin corticotropin creatinine hydrocortisone ketoconazole retinoic acid animal experiment animal model article controlled study corticotropin blood level creatinine urine level Cushing disease dog drug efficacy drug safety female hormone blood level hydrocortisone urine level hypophysis hypophysis adenoma male nonhuman nuclear magnetic resonance imaging priority journal survival tumor volume Adenoma Adrenocorticotropic Hormone alpha-MSH Animals Body Weight Creatinine Dog Diseases Dogs Female Hydrocortisone Ketoconazole Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Pituitary Gland Pituitary Neoplasms Survival Rate Tretinoin Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action in dogs with Cushing's disease. A randomized treatment with retinoic acid (n = 22) vs. ketoconazole (n = 20) in dogs with Cushing's disease was assigned for a period of 180 d. Clinical signs, plasma ACTH and α-MSH, the cortisol/creatinine urine ratio, and pituitary magnetic resonance imaging were assessed and compared at different time points. We recorded a significant reduction in plasma ACTH and α-MSH, and also in the cortisol/ creatinine urine ratio, of the dogs treated with retinoic acid. Pituitary adenoma size was also significantly reduced at the end of retinoic acid treatment. Survival time and all the clinical signs evaluated showed an improvement in the retinoic-acid-treated dogs. No adverse events or signs of hepatotoxicity were observed, suggesting that the drug is not only effective but also safe. Retinoic acid treatment controls ACTH and cortisol hyperactivity and tumor size in dogs with ACTH-secreting tumors, leading to resolution of the clinical phenotype. This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease. Copyright © 2006 by The Endocrine Society. Fil:Giacomini, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Páez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Labeur, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v147_n9_p4438_Castillo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	alpha intermedin corticotropin creatinine hydrocortisone ketoconazole retinoic acid animal experiment animal model article controlled study corticotropin blood level creatinine urine level Cushing disease dog drug efficacy drug safety female hormone blood level hydrocortisone urine level hypophysis hypophysis adenoma male nonhuman nuclear magnetic resonance imaging priority journal survival tumor volume Adenoma Adrenocorticotropic Hormone alpha-MSH Animals Body Weight Creatinine Dog Diseases Dogs Female Hydrocortisone Ketoconazole Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Pituitary Gland Pituitary Neoplasms Survival Rate Tretinoin
spellingShingle	alpha intermedin corticotropin creatinine hydrocortisone ketoconazole retinoic acid animal experiment animal model article controlled study corticotropin blood level creatinine urine level Cushing disease dog drug efficacy drug safety female hormone blood level hydrocortisone urine level hypophysis hypophysis adenoma male nonhuman nuclear magnetic resonance imaging priority journal survival tumor volume Adenoma Adrenocorticotropic Hormone alpha-MSH Animals Body Weight Creatinine Dog Diseases Dogs Female Hydrocortisone Ketoconazole Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Pituitary Gland Pituitary Neoplasms Survival Rate Tretinoin Castillo, V. Giacomini, D. Páez-Pereda, M. Stalla, J. Labeur, M. Theodoropoulou, M. Holsboer, F. Grossman, A.B. Stalla, G.K. Arzt, E. Retinoic acid as a novel medical therapy for Cushing's disease in dogs
topic_facet	alpha intermedin corticotropin creatinine hydrocortisone ketoconazole retinoic acid animal experiment animal model article controlled study corticotropin blood level creatinine urine level Cushing disease dog drug efficacy drug safety female hormone blood level hydrocortisone urine level hypophysis hypophysis adenoma male nonhuman nuclear magnetic resonance imaging priority journal survival tumor volume Adenoma Adrenocorticotropic Hormone alpha-MSH Animals Body Weight Creatinine Dog Diseases Dogs Female Hydrocortisone Ketoconazole Magnetic Resonance Imaging Male Pituitary ACTH Hypersecretion Pituitary Gland Pituitary Neoplasms Survival Rate Tretinoin
description	Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action in dogs with Cushing's disease. A randomized treatment with retinoic acid (n = 22) vs. ketoconazole (n = 20) in dogs with Cushing's disease was assigned for a period of 180 d. Clinical signs, plasma ACTH and α-MSH, the cortisol/creatinine urine ratio, and pituitary magnetic resonance imaging were assessed and compared at different time points. We recorded a significant reduction in plasma ACTH and α-MSH, and also in the cortisol/ creatinine urine ratio, of the dogs treated with retinoic acid. Pituitary adenoma size was also significantly reduced at the end of retinoic acid treatment. Survival time and all the clinical signs evaluated showed an improvement in the retinoic-acid-treated dogs. No adverse events or signs of hepatotoxicity were observed, suggesting that the drug is not only effective but also safe. Retinoic acid treatment controls ACTH and cortisol hyperactivity and tumor size in dogs with ACTH-secreting tumors, leading to resolution of the clinical phenotype. This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease. Copyright © 2006 by The Endocrine Society.
format	Artículo Artículo publishedVersion
author	Castillo, V. Giacomini, D. Páez-Pereda, M. Stalla, J. Labeur, M. Theodoropoulou, M. Holsboer, F. Grossman, A.B. Stalla, G.K. Arzt, E.
author_facet	Castillo, V. Giacomini, D. Páez-Pereda, M. Stalla, J. Labeur, M. Theodoropoulou, M. Holsboer, F. Grossman, A.B. Stalla, G.K. Arzt, E.
author_sort	Castillo, V.
title	Retinoic acid as a novel medical therapy for Cushing's disease in dogs
title_short	Retinoic acid as a novel medical therapy for Cushing's disease in dogs
title_full	Retinoic acid as a novel medical therapy for Cushing's disease in dogs
title_fullStr	Retinoic acid as a novel medical therapy for Cushing's disease in dogs
title_full_unstemmed	Retinoic acid as a novel medical therapy for Cushing's disease in dogs
title_sort	retinoic acid as a novel medical therapy for cushing's disease in dogs
publishDate	2006
url	http://hdl.handle.net/20.500.12110/paper_00137227_v147_n9_p4438_Castillo
work_keys_str_mv	AT castillov retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT giacominid retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT paezperedam retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT stallaj retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT labeurm retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT theodoropouloum retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT holsboerf retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT grossmanab retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT stallagk retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs AT arzte retinoicacidasanovelmedicaltherapyforcushingsdiseaseindogs
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Retinoic acid as a novel medical therapy for Cushing's disease in dogs

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